title: Significance of the D-serine-deaminase and D-serine metabolism of Staphylococcus saprophyticus for virulence.
abstract: Staphylococcus saprophyticus is the only species of Staphylococcus that is typically uropathogenic and possesses a gene coding for a D-serine-deaminase (DsdA). As D-serine is prevalent in urine and toxic or bacteriostatic to many bacteria, it is not surprising that the D-serine-deaminase gene is found in the genome of uropathogens. It has been suggested that D-serine-deaminase or the ability to respond to or to metabolize D-serine is important for virulence. For uropathogenic Escherichia coli (UPEC), a high intracellular D-serine concentration affects expression of virulence factors. S. saprophyticus is able to grow in the presence of high D-serine concentrations; however, its D-serine metabolism has not been described. The activity of the D-serine-deaminase was verified by analyzing the formation of pyruvate from D-serine in different strains with and without D-serine-deaminase. Cocultivation experiments were performed to show that D-serine-deaminase confers a growth advantage to S. saprophyticus in the presence of D-serine. Furthermore, in vivo coinfection experiments showed a disadvantage for the ΔdsdA mutant during urinary tract infection. Expression analysis of known virulence factors by reverse transcription-quantitative PCR (RT-qPCR) showed that the surface-associated lipase Ssp is upregulated in the presence of D-serine. In addition, we show that S. saprophyticus is able to use D-serine as the sole carbon source, but interestingly, D-serine had a negative effect on growth when glucose was also present. Taken together, D-serine metabolism is associated with virulence in S. saprophyticus, as at least one known virulence factor is upregulated in the presence of D-serine and a ΔdsdA mutant was attenuated in virulence murine model of urinary tract infection.
authors.affiliation: Department of Medical Microbiology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Korte-Berwanger
authors.forename: Türkan
authors.initials: T
authors.lastname: Sakinc
authors.forename: Kimberly
authors.initials: K
authors.lastname: Kline
authors.forename: Hailyn V
authors.initials: HV
authors.lastname: Nielsen
authors.forename: Scott
authors.initials: S
authors.lastname: Hultgren
authors.forename: Sören G
authors.initials: SG
authors.lastname: Gatermann
mesh_terms: D000641:Ammonia / Q000378:metabolism; D000818:Animals; D005260:Female; D006836:Hydro-Lyases / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D019289:Pyruvic Acid / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000378:metabolism* / Q000382:microbiology; D057790:Staphylococcus saprophyticus / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D014552:Urinary Tract Infections / Q000378:metabolism* / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D037521:Virulence Factors; D012694:Serine; D000641:Ammonia; D019289:Pyruvic Acid; D006836:Hydro-Lyases; C101950:D-serine dehydratase